title: Fluorescence in situ hybridization characterization of new translocations involving TEL (ETV6) in a wide spectrum of hematologic malignancies.
abstract: The ETV6 (also known as TEL) gene on chromosome 12p13 is the target of a number of translocations associated with various hematologic malignancies. The contribution of ETV6 to leukemogenesis occurs through different mechanisms that involve either its helix-loop-helix dimerization domain or its E26 transformation-specific (ETS) DNA-binding domain. Using fluorescence in situ hybridization we characterized seven new ETV6 rearrangements in chronic myeloid leukemia, acute myeloid leukemia, acute lymphoblastic leukemia, and non-Hodgkin's lymphoma. These aberrations, not always discernible at the cytogenetic level, include a t(5;12)(q31;p13), t(6;12;17)(p21;p13;q25), t(7;12)(p15;p13), t(7;12)(p12;p13), t(7;12)(q36;p13), t(12;13)(p13;q12), and a not completely defined t(12;?)(p13;?). Loss or disruption of the second ETV6 allele by a del(12)(p12p13) or by an intragenic ETV6 deletion was detected in two cases. In six cases the 12p13 breakpoint occurred in the 5' end of ETV6, upstream to exons encoding the HLH domain, whereas the remaining case had a breakpoint between the exons coding for the HLH domain and the exons coding for the ETS domain of ETV6. These observations provide further evidence for the multiple contributions of ETV6 in the pathogenesis of a wide range of hematologic malignancies.
authors.affiliation: Center for Human Genetics and Flanders Interuniversity Institute of Biotechnology, University of Leuven, Leuven, Belgium.
authors.forename: I
authors.initials: I
authors.lastname: Wlodarska
authors.forename: R
authors.initials: R
authors.lastname: La Starza
authors.forename: M
authors.initials: M
authors.lastname: Baens
authors.forename: J
authors.initials: J
authors.lastname: Dierlamm
authors.forename: A
authors.initials: A
authors.lastname: Uyttebroeck
authors.forename: D
authors.initials: D
authors.lastname: Selleslag
authors.forename: A
authors.initials: A
authors.lastname: Francine
authors.forename: C
authors.initials: C
authors.lastname: Mecucci
authors.forename: A
authors.initials: A
authors.lastname: Hagemeijer
authors.forename: H
authors.initials: H
authors.lastname: Van den Berghe
authors.forename: P
authors.initials: P
authors.lastname: Marynen
mesh_terms: D000293:Adolescent; D000368:Aged; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D002881:Chromosomes, Human, Pair 12; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D019337:Hematologic Neoplasms / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins; D014157:Transcription Factors / Q000235:genetics*; D014178:Translocation, Genetic; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins; D014157:Transcription Factors; D000097764:ETS Translocation Variant 6 Protein